Escitalopram is the active S-enantiomer of citalopram. In a chronic mild stress model of depression in rats, treatments with both escitalopram and citalopram were effective; however, a faster time to onset of efficacy compared to vehicle treatment was observed for escitalopram-treated (5 mg/kg/day) than for citalopram-treated (10 mg/kg/day) rats at Week 1. To study the predictability of this observation in the clinic, we analysed 4-week data from an 8-week, double-blind, randomised, placebo-controlled, flexible-dose study that compared escitalopram and citalopram to placebo in primary care patients with major depressive disorder (baseline Montgomery and Asberg Depression Rating Scale (MADRS) scores > or =22 and < or =40). Since the flexible dosing started after Week 4, analysis of 4-week data ensured that the patients received fixed doses of 10 mg/day escitalopram (155 patients), 20 mg/day citalopram (160 patients), or placebo (154 patients). The efficacy analysis showed a significantly superior therapeutic effect for escitalopram versus placebo from Week 1 onwards (observed cases) with an adjusted mean change in MADRS at Week 4 (last observation carried forward) of 2.7 points (P=0.002). By comparison, 20 mg/day citalopram did not demonstrate a statistically significant effect compared to placebo. Escitalopram was well tolerated with an adverse event profile similar to that of citalopram. The preclinical observation that escitalopram possesses a faster time to onset of efficacy than citalopram was also seen in primary care patients with major depressive disorder. Thus, escitalopram is efficacious in depression and the effect occurs earlier than for citalopram.
Hyperdynamic circulation, systolic and diastolic left ventricular dysfunction and certain electrophysiological abnormalities have been associated with cirrhosis and known for a long time. These clinical features have been introduced as cirrhotic cardiomyopathy (CCM), which is characterized by blunted myocardial contractile responsiveness to physical, physiological and pharmacological stress. Importantly, cardiac dysfunction can be reversible and can improve due to effective medical treatment and also after liver transplantation. Echocardiography and electrocardiography are essential tools for recognizing the characteristic changes in the myocardial function and also the alterations in the electrophysiological properties of the heart. Laboratory markers are auxiliary modalities further aiding the establishment of the correct diagnosis. In this review, we aimed to collect the pathophysiological background and clinical characteristics of CCM with the intention of summarizing the current possibilities for the diagnosis establishment and treatment of this cardio-hepatic disorder.Abbreviations: A: late diastolic transmitral peak flow velocity; ACE: angiotensin converting enzyme; ANP: atrial natriuretic peptide; ARB: angiotensin receptor blocker; BNP: brain natriuretic peptide; cAMP: cyclic adenosine monophosphate; CCM: cirrhotic cardiomyopathy; CGRP: calcitonin gene-related peptide; CO: carbon monoxide; DD: diastolic dysfunction; DT: deceleration time; E: early diastolic transmitral peak flow velocity; Ea: early diastolic velocity of the septal mitral annulus; EF: ejection fraction; MUGA: Multi Gated Acquisition Scan; NO: nitric oxide; NSBB: non-selective beta-blocker; pro-BNP: pro-brain natriuretic peptide; QTc: corrected QT interval; RAAS: renin-angiotensin aldosterone system; RALES: Randomized Aldactone Evaluation Study; suPAR: urokinase-type plasminogen activator receptor; TDI: Tissue Doppler Imaging; TIPS: transjugular intrahepatic portosystemic shunt; TNF-alpha: tumor necrosis factor-alpha.
Escitalopram is the active S-enantiomer of citalopram. In a chronic mild stress model of depression in rats, treatments with both escitalopram and citalopram were effective; however, a faster time to onset of efficacy compared to vehicle treatment was observed for escitalopram-treated (5 mg/kg/day) than for citalopram-treated (10 mg/kg/day) rats at Week 1. To study the predictability of this observation in the clinic, we analysed 4-week data from an 8-week, doubleblind, randomised, placebo-controlled, flexible-dose study that compared escitalopram and citalopram to placebo in primary care patients with major depressive disorder (baseline Montgomery and Åsberg Depression Rating Scale (MADRS) scores Ø22 and AE40). Since the flexible dosing started after Week 4, analysis of 4-week data ensured that the patients received fixed doses of 10 mg/day escitalopram (155 patients), 20 mg/day citalopram (160 patients), or placebo (154 patients). The efficacy analysis showed a significantly superior therapeutic effect for escitalopram versus placebo from Week 1 onwards (observed cases) with an adjusted mean change in MADRS at Week 4 (last observation carried forward) of 2.7 points (PΩ0.002). By comparison, 20 mg/day citalopram did not demonstrate a statistically significant effect compared to placebo. Escitalopram was well tolerated with an adverse event profile similar to that of citalopram. The preclinical observation that escitalopram possesses a faster time to onset of efficacy than citalopram was also seen in primary care patients with major depressive disorder. Thus, escitalopram is efficacious in depression and the effect occurs earlier than for citalopram.Currently, citalopram is one of the most widely prescribed antidepressants. It is a potent, highly selective serotonin reuptake inhibitor with high affinity for serotonin reuptake sites and low affinity for noradrenaline and dopamine reuptake sites. Citalopram exists as a chiral compound that is a racemic mixture of R-and S-enantiomers in a 1:1 ratio. Escitalopram, the active S-enantiomer of citalopram, mediates serotonin reuptake inhibition (Hyttel et al. 1992;Owens et al. 2001) and antidepressant activity (Hogg & Sánch-ez 1999), and has increased selectivity and potency compared to citalopram.Depression is a very common and widespread disorder with an estimated lifetime prevalence of 16 to 17% in both Europe and the United States (Kessler et al. 1994;Lépine et al. 1997). According to the World Health Organisation (Murray & Lopez 1997), depression is now associated with more years of disability than any other chronic disorder. Some common complicating factors in the treatment of depression are that the therapy itself may be associated with adverse drug reactions or it may fail to alleviate the condition. There is an unmet need for improvements to the currently available drugs with some of the key areas for improvement being: faster onset of action than current ther- apies, increase of the proportion of patients who respond to treatment, better long-term ef...
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